Objective: To investigate miR-146a's role in cartilage repair in osteoarthritis of the first metatarsophalangeal joint (OFMJ). Methods: The serum samples of 30 OFMJ patients diagnosed in our hospital and 30 healthy people receiving physical examination were enrolled. The expression of miR-146a in those subjects was measured by qRT-PCR. Articular cartilage cells were isolated and transfected with lentivirus to silence or overexpress miR-146a. RT-PCR was performed to detect the transfection efficiency and the content of inflammatory factors. CCK-8 assay was to test cell proliferation activity and TUNEL assay was to detect cell apoptosis. The expressions of genes and proteins related to apoptosis and the TGF- β1/Smads signaling pathway were determined by RTPCR and Western blotting. Results: The serum miR-146a level in the patients with osteoarthritis of the first metatarsophalangeal joint was decreased significantly (p < 0.05). miR-146a showed a high expression in mimics group and was significantly lower in inhibitors group. The content of inflammatory factors in miR-146a mimics group was significantly reduced compared with other two groups (p < 0.05), and significantly higher level of inflammatory factors was detected in miR-146a inhibitors group (p < 0.05) along with increased number of cells and proliferation activity (p < 0.05) as well as increased cell apoptosis (p < 0.05). Bcl-2 was upregulated in miR-146a mimics group and Caspase-3 level was decreased. The expression of TGF-β 1/Smads was elevated in miR146a inhibitors group. Conclusion: MiR-146a can participate in the cartilage repair in osteoarthritis of the first metatarsophalangeal joint possibly through regulating TGF-β1/Smads signaling pathway.